coagulation Flashcards
what is coagulation?
- process by which blood changes from a liquid into a blood clot
- causes the cessation of blood from a blood vessel
what does the coagulation process involve?
- activation
- adhesion
- aggregation of platelets
- deposition of fibrin
what can coagulation be divided into?
- primary haemostasis: formation of a platelet plus
- secondary haemostasis: activation of clotting cascade, results in production of fibrin to strengthen platelet plug
what are the 3 separate stages to haemostasis?
- vascular phase
- platelet phase
- coagulation phase
what happens in the vascular phase?
- damage to blood vessel wall will cause contraction in that area
- occurs due to damage to endothelial cells
- damage causes them to release various factors
what are the various factors that are released?
- ADP
- TF (factor 3): need for activation of thrombin from prothrombin
- prostacyclin
- endothelins: stimulate SM contraction, stimulate cell division of endothelial cells, SM cells and fibroblasts –> aid repair of damaged site
what also happens to endothelial cells in this phase?
- become sticky
- express surface proteins
- these allow them to stick to other endothelial cells
- attempt to close damaged area
what do platelets contain?
- actin and myosin (able to contract)
- no nucleus
- large ER and golgi apparatus for storage of Ca ions
- plenty of mitochondria for ATP formation
what do platelets produce?
- prostaglandins
- fibrin-stabilising factor
- PDGF (helps vascular repair)
- thromboxane A2 (prominent vasoconstrictor)
describe the membrane of platelets
- special glycoprotein membrane
- prevents adhesion to normal epithelium
- promotes adhesion to damaged epithelium
- particularly adherent to collagen
what is a low platelet count called? what causes it?
thrombocytopaenia
- high platelet destruction
- low platelet production
what is a high platelet count called? what causes it?
thrombocytosis
- inc. platelet formation
- seen in response to infection, inflammation, cancer
what is platelet formation controlled by?
TPO (thrombopoietin) made in liver
when does the platelet phase begin?
as soon as platelets begin to attach themselves to damaged areas of endothelium
when a platelet becomes attached to a damaged endothelial surface, what happens?
- changes its own shape and size
- will swell
- become large and irregular
- contractile proteins contract causing the release of granules
- ADP, thromboxane, Ca ions released
what are the 2 types of granule released by platelets?
- alpha: contain GF e.g. fibrinogen and PDGF
- dense: contain non-protein things e.g. thromboxnae, serotonin, adrenaline, histamine, Ca, ATP
what is fibrin? what produces it?
- activated form of fibrinogen
- produced by liver/ platelets
- activated in clotting and forms lots of fibrin threads
- activated fibrin will entangle fibrin and put RBCs into ball
what are the 2 separate clotting pathways?
- intrinsic pathway
- extrinisc pathway
- eventually join to form common pathway
describe the intrinsic pathway
- begins in blood stream
- activated when blood is exposed to collagen
- F12 is activated by exposed collagen
- F12a activates F11
- F11a combines with Ca and activated F9
- at same time, platelets release PF3 and F8 is activated
- F9a and F8a form F10 activating factor (tenase)
describe the extrinsic pathway
- begins in vessel wall
- damaged endothelial cells release F3 (tissue factor)
- TF combines with Ca and activates F7
- F7a-TF complex quickly inactivated by antithrombin III
describe the first part of the common pathway, where thrombin gets activated
- F10 is activated by F7a or tenase
- forms F10a (prothrombinase)
- F10a with Ca ions and 5a convert prothrombin into thrombin
- thrombin = F2a
what is the relevance of F5 in this step?
not required for this step but when present inc. rate
what does thrombin then do?
- activate fibrinogen to firbin
- fibrin strands join together
- with help of F13a it causes cross-linking of fibrin strands
what is F13 activated by? what is it also known as?
- activated by thrombin
- fibrin stabilising factor
what is the difference in pathways with the levels of thrombin?
- extrinsic produces thrombin v. quickly but in small amounts
- intrinsic pathway produces large amount of thrombin, takes a while to get going
What is tissue factor pathway inhibitor?
- directly inhibits F10a
- important in regulating clotting cascade
what is antithrombin-III?
enzymes found circulating in blood that binds to thrombin, prevents its action
what does activated fibrin do to thrombin?
- will remove and inactivate thrombin
- 90% thrombin produced inactivated in this way
